Impact of Signet-Ring Cell Histology in the Management of Patients with Non-Metastatic Gastric Cancer: Results from a Retrospective Multicenter Analysis Comparing FLOT Perioperative Chemotherapy vs. Surgery Followed by Adjuvant Chemotherapy

Abstract

Background: FLOT perioperative chemotherapy represents the standard of care in non-metastatic gastric cancer patients. Signet-ring cell positivity is associated with a worse prognosis in patients with gastric cancer treated with chemotherapy. Comparison between FLOT perioperative chemotherapy vs. surgery followed by adjuvant chemotherapy based on signet-ring cell positivity is lacking. The aim of the analysis was to compare perioperative FLOT with adjuvant chemotherapy in gastric cancer patients stratified by signet-ring cell positivity. Methods: We conducted a retrospective multicenter analysis based on disease-free survival (DFS) and overall survival (OS) in patients with gastric cancer who received perioperative chemotherapy with a FLOT regimen and compared their survival with a historical cohort of patients treated with adjuvant chemotherapy, matched by cT and cN stage and by tumor histological features. Results: Seventy-six patients were enrolled and 24 (32%) were signet-ring cell positive. At a median follow-up time of 39 months, the median DFS was 26.3 months and the median OS was 37.3 months. Signet-ring cell positivity was associated with a shorter OS (median OS: 20.4 vs. 46.9 months, HR: 3.30, 95%CI: 1.56–6.99, p = 0.0018) and DFS (mDFS: 15.2 vs. 38.6 months, HR: 3.18, 95%CI: 1.55–6.54, p = 0.0016). This was confirmed by multivariate analysis for DFS (Exp(B): 2.55) and OS (Exp(B): 2.68). After propensity score matching, statistically significant shorter DFS (HR: 3.30, 95%CI: 1.50–7.35, p = 0.003) and OS (HR: 5.25, 95%CI: 2.18–12–68, p = 0.0002) were observed for patients with signet-ring cell positivity who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy. Conclusions: Signet-ring positivity was associated with shorter DFS and OS in patients who received perioperative treatment with FLOT compared with surgery followed by adjuvant therapy. These data suggest that for patients with signet-ring cell histology, FLOT perioperative treatment might not always be the best choice of treatment, and further research should be focused on this group of patients.

A retrospective study of adjuvant albumin-bound paclitaxel plus S-1 after D2 gastrectomy versus oxaliplatin plus S-1 in gastric cancer

“…While in our study, there were 17 DGC in the AS group, the median 3-year DFS was 48.9 m, with a 3-DFS rate of 75.3%. Signet-ring positive GC was reported with a poor median DFS of 26.3 months 19 . There were 14 signet-ring positive patients in AS group of our study, which had a prolonged DFS compared with the SOX group (40.0 vs 13.8 m, p = 0.02).…”

“…A neoadjuvant approach for GC has been found to be more effective than surgery alone at reducing tumor burden, assessing tumor response, and improving DFS by the large phase III clinical studies such as FLOT4 16 , 17 , PRODIGY 18 and RESOLVE studies 7 . Recently, a statistically significant shorter DFS (HR: 3.30, 95%CI 1.50–7.35, p = 0.003) were observed for patients with signet-ring cell positive who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy 19 . As a retrospective study, it indicated that new postoperative protocols for special types of GC such as signet-ring cell positive are still unsatisfactory.…”